Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2.

As one of the earliest identified susceptible animals for the SARS-CoV-2, cats are also the vulnerable hosts for feline coronaviruses, ie feline enteric coronavirus (FECV). Here, to understand the cross-presentation of coronavirus-derived peptides by cat major histocompatibility complex molecule feline leucocyte antigen (FLA) class I, unpredictable natural peptide motifs presented by FLA-K*00701 and FLA-E*00301 were identified through peptide elution and further confirmed by the structural determination of the 2 FLA class I molecules. Based on these precise motifs of FLA class I peptides, the atlas of cross-presenting peptides from different coronaviruses in cats were sketched with 3 hotspots in C-terminal half of ORF1ab protein. The possibility of cross-presentation is further supported by the similar conformation of the corresponding peptides KP-CoV-9 (RSFIEDLLF) and KM-FECV-9 (RSAVEDLLF) from the 2 coronaviruses presented by FLA-K*00701. Our findings provide insights into the understanding of the cross-presentation of peptides from SARS-CoV-2 and feline coronaviruses FECV and the development of universal vaccine for coronaviruses.